We have characterized mice with TNF ablation in macrophages/neutrophils, T cells or B cells in several pathophysiological models. We are in the process of generating a similar panel for LTa cytokine. TNF produced by T cells plays an important and non-redundant role in both host defense (Listeria, TB) and in autoimmune liver injury induced by ConA. Ablation of either TNF, or LTa fails to modulate the frequency of spontaneous tumors in mice with p53 null background, suggesting that increased frequency of lymphoma in patients on continuous TNF blockers may not be directly related to TNF.